Therapeutic drug monitoring of posaconazole in patients with acute myeloid leukemia or myelodysplastic syndrome.

Posaconazole is a broad-spectrum triazole antifungal available as an oral suspension. Pharmacokinetic data showed a high variability of plasma posaconazole concentrations (PPCs) in patients, suggesting a potential interest in drug monitoring. The aim of our prospective study was to measure the PPCs in prophylactically treated patients to evaluate the impact of different factors on these concentrations. In 40 patients treated prophylactically with posaconazole for acute myeloid leukemia or myelodysplastic syndrome between February 2009 and August 2010, PPCs were measured at day 7 of treatment and then twice weekly. Demographic data, clinical data (including gastrointestinal disorders, comedications, and treatment compliance), caloric and fat intake, and biological data were collected and evaluated. We obtained 275 measurements of PPCs, with a median of 430 ng/ml. PPCs were significantly lower in patients with mucositis (P < 0.001), nausea (P = 0.03), diarrhea (P = 0.03), or vomiting (P = 0.05). PPCs were higher in patients with a higher caloric intake (P = 0.02), while the proportion of fat intake had no influence on PPCs (P = 0.84). The concomitant use of proton pump inhibitors decreased the PPCs (P = 0.02), while the use of tacrolimus increased the PPC (P = 0.03). In the multivariate analysis, the factors influencing the PPCs independently were the concomitant use of tacrolimus (P < 0.001), the presence of mucositis (P = 0.01), and food intake (P = 0.02). Our study confirmed the high variability of posaconazole bioavailability and showed the significant influence of gastrointestinal disorders, food intake, and concomitant medication on the PPCs. However, the optimal PPCs still remain to be defined and correlated with clinical efficacy.

[Mastocytosis: revisited with new cytogenetic data]. / La mastocytose: une maladie revisitée a la lumière des nouvelles données génétiques.

Mastocytosis is a heterogenous disorder due to abnormal proliferation and infiltration of mast cells in different tissues, primarily the skin and the bone marrow. Cutaneous mastocytosis is often benign and regresses spontaneously. Systemic mastocytosis is a chronic disease in which some types are indolent but other types such as mast cell leukemia are very aggressive. Pathogenesis of systemic mastocytosis involves a somatic mutation of the gene coding for the c-kit receptor, the most frequent mutation being D816V. Diagnostic criteria have been established by the WHO using histopathological, molecular and biochemical parameters. Treatment of systemic mastocytosis remains a challenge for the clinician due to variability and complexity of the disease. There is, in addition, a lack of a standard and efficient treatment. New targeted therapies with tyrosine kinase inhibitors directed against the c-kit receptor are currently being studied, with the purpose to act specifically on the " primum movens "of the disease. The current review provides an overview of pathogenesis, clinical presentation, diagnosis and classification of cutaneous and systemic mastocytosis. We also discuss the prognosis and the different treatments currently available according to the sub-type of mastocytosis.

A carotid artery dissection presenting with dysphagia due to a dilation of upper oesophagus.

Carotid and vertebral artery dissection is one of the major causes of ischemic stroke in young patients and diagnosing it remains a challenge for the clinician due to its variable clinical presentation. We report the case of a 57-years old man admitted to the emergency department complaining of dysphagia and a hoarse voice. Physical examination revealed a left deviation of his tong and some weakness of the left side of his soft palate. A gastroscopy and a cervical tomodensitometry revealed the presence of an important dilation of his upper oesophagus. A cerebral magnetic resonance was performed, showing en excentric high signal intensity on the left carotid artery, and the MR angiography confirmed the presence of an acute dissection on the left internal carotid artery. Our patient suffered of a left carotid artery dissection presenting with ipsilateral Xth and XIIth nerve palsies. His main symptom was a dysphagia due to a dilation of his upper oesophagus; the pneumogastric nerve being responsible for the parasympathic innervation of the upper muscles of the oesophagus.

Autoimmune polyendocrine syndrome and thrombocytosis.

We describe a woman aged 37  years, affected with Hashimoto's thyroiditis, detected since the age of 17, with gonadic insufficiency with anti-ovarian antibodies since the age of 22  years and Addison's disease since 24  years old. At that moment, the diagnosis of autoimmune polyendocrine syndrome (APS) was made. Concomitant to this diagnosis, thrombocytosis was detected and aetiological assessment revealed an atrophy of the spleen. Differential diagnoses of APS and hyposplenism will be discussed. We will look at a possible association between these two pathologies. Indeed, asplenism is found in approximately 20% of adults affected by type 1 APS, also called auto-immune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) syndrome. The most likely aetiology for this atrophy of the spleen is a destruction of auto-immunological origin. However, in our patient, the search for a mutation of the autoimmune regulator (AIRE) gene proved negative. This mutation is commonly, but not systematically, present in type 1 APS. A type 2 APS should then be considered.

Multiple infection of Hydrobia stagnorum (Gmelin) with larval Trematodes.

Analysis of double infections of Hydrobia stagnorum (Gmelin) with larval trematodes leads to the following conclusions: 1.--negative interaction occurs when both species have the same precercarial stage (rediae or sporocysts); 2.--negative interaction is generally absent when these precercarial stages are different (redia + sporocyst); 3.--the few exceptions on 2. could be a result of predation by the redia on the sporocyst; 4.--the negative interactions are most likely the result of competition for the same type of food.